Standard operating procedure
Title: Review of orphan designation at the time of granting/varying a marketing authorisation
Status: Public
Document no.: SOP/H/3190
Lead author
Approver
Effective date: 9-FEB-16
Name: Agnieszka Wilk-
Name: Kristina Larsson
Review date: 9-FEB-19
Signature: ON FILE
Supersedes:
Kachlicka
Signature: ON FILE
SOP/H/3190 (22-MAY-2015 TW
3401)
Date: 9-FEB-16
Date: 9-FEB-16
TrackWise record no.: 4642
1. Purpose
This SOP describes the procedure for reviewing the orphan designation at the time of the initial
authorisation of an orphan medicinal product, or an extension of indication (type II variation) for a
designated orphan product with a new orphan condition. The procedure runs in parallel with the
adoption of the opinion by the CHMP and the granting of or variation to a marketing authorisation by
the European Commission.
2. Scope
This SOP applies to:

Committees Secretariat Service in Scientific Committee Support Department in Procedure
Management and Committees Support Division

Legal Department

Medical and Health Information Service in Communication Department in Stakeholders and
Communication Division

Orphan Medicines Office in Human Medicines in Product Development Scientific Support
Department, Regulatory, Science and Innovation Support Department in Human Medicines
Research and Development Support Division

Procedure Management Department in Procedure Management and Committees Support Division

Regulatory Affairs Office in Regulatory, Science and Innovation Support Department in Human
Medicines Research and Development Support Division
30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom
Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555
Send a question via our website www.ema.europa.eu/contact
An agency of the European Union
© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.
3. Responsibilities
It is the responsibility of each Head of Office/Service to ensure that this procedure is adhered to within
their office/service. The responsibility for the execution of a particular part of this procedure is
identified in the right-hand column of section 9.
4. Changes since last revision

Introduction of two deadlines for submission of maintenance report: at time of submission of CHMP
application (for accelerated review and type II variation) or at day 121 for regular MA procedure

Introduction of pre-assessment TC with sponsor

Removal of validation of the sponsor’s maintenance report

Introduction of quality check of the review reports by HoO

Sending oral explanation invitations to sponsors following CHMP opinion

Introduction of negative opinions check by AF-LD and D-RS-REA
5. Documents needed for this SOP

Template 1a - Request for report on maintenance of orphan designation at time of MA (located at
X:\Templates\Others\OD Post COMP)

Template 1b - Request for updated report on maintenance of orphan designation at time of MA
(located at X:\Templates\Others\OD Post COMP)

Template 2 - Report on maintenance of orphan designation at time of MA - receipt confirmation
(located at X:\Templates\Others\OD Post COMP)

Template 3a - Review of OD at MA - EMA-COMP report (located at X:\Templates\Others\OD
Database\Review of OD at MA - EMA-COMP report)

Template 3b - Presentation on review (located at X:\Templates\Others\OD Post COMP)

Template 3c – Eudralink message for sending LoQ and invitation to oral hearing (located at
X:\Templates\Others\OD Post COMP)

Template 4a – COMP coordinator’s comments on review (located at X:\Templates\Others\OD Post
COMP)

Template 4b – COMP coordinator’s reader’s guidance on review (located at
X:\Templates\Others\OD Post COMP)

Template 5a - Review of OD at MA – positive opinion (located at X:\Templates\Others\OD
Database)

Template 5b - Review of OD at MA – negative opinion (located at X:\Templates\Others\OD
Database)

Template 6a - Review of OD at MA – opinion to EC outcome (located at X:\Templates\Others\OD
Post COMP)
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
Template 6b - Review of OD at MA – opinion to sponsor outcome (located at
X:\Templates\Others\OD Post COMP)

Template 6c - Template letter informing sponsor on outcome (located at X:\Templates\Others\OD
Post COMP\Review of OD at MA – negative opinion to sponsor)

Template 6d - Template letter informing sponsor on outcome (located at X:\Templates\Others\OD
Post COMP\Review of OD at MA – sponsor notified of final negative opinion to EC)
6. Related documents

SOP/H/3004 on tasks of the product team on the handling of the initial marketing authorisation
application

SOP/H/3046 on preparation of the public summary of opinion for orphan medicinal product
designation

SOP/H/3049 on orphan medicinal product designation

SOP/H/3371 on preparation and publication of the public summary of opinion on the review of
orphan designation at the time of marketing authorisation

WIN/H/3047 on checking-in of applications for orphan designation

Communication from the Commission on Regulation (EC) No 141/2000 of the European Parliament
and of the Council on orphan medicinal products (2003/C 178/02)
http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2003:178:0002:0008:en:PDF

Procedural advice
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_00039
2.jsp&mid=WC0b01ac058061f019

Sponsor’s report on the maintenance of the designation criteria at the time of marketing
authorisation application for a designated orphan medicinal product (template):
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2015/02
7. Definitions
AF-LD
Legal Department
CHMP application
In the context of this SOP, use of the term applies to the initial marketing
authorisation application or to a type II variation (extension of indication)
application for a new indication covered by an orphan product designation
CHMP
Committee for Medicinal Products for Human Use
COMP Co
COMP Co-ordinator
COMP Sec
COMP Secretariat (in C-CS-SCS)
COMP
Committee for Orphan Medicinal Products
C-PM
Procedure Management Department in Procedure Management and
Committees Support Division
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D-DS-OME
Orphan Medicines Office in Product Development Scientific Support Department
in Human Medicines Research and Development Support Division
DREAM
Document records electronic archive management
D-RS-REA
Regulatory Affairs Office in Regulatory, Science and Innovation Support
Department in Human Medicines Research and Development Support Division
EC
European Commission
EudraLink
The European medicines regulatory network’s secure file-transfer system used
for exchanging information for regulatory purposes
LoQ
List of questions
MA
Marketing authorisation
MHI writer
Medical writer (in S-CO-MHI)
MMD
Managing meeting documents system
OME Asst
Assistant (in D-DS-OME)
OME Co
Co-ordinator (scientific officer in D-DS-OME)
OME HoO
Head of Orphan Medicines Office (in D-DS-OME)
OME line listing
Tabular information on MAA application for orphan medicines prepared by DDS-OME updated monthly and tabled in MMD for COMP meetings
PM
Product manager (in C-PM)
S-CO-MHI
Medical and Health Information Service, Communication Department in
Stakeholders and Communication Division
SIAMED
Product information and application tracking system
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8. Process map/ flow chart
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9. Procedure

Declarations of interest are checked and evaluated for all staff before involvement according to
SOP/EMA/0101 and SOP/EMA/0040 listed under “Related documents”.

All messages containing confidential information must be sent via EudraLink.

All procedural timelines and application guidance are published on the EMA website.

Unless no longer available, COMP Co and OME Co remain the same as per orphan designation
procedure.

CHMP procedural timelines mentioned below apply to the assessment of an initial MA application.
In the case of extension of indications (type II variations), the timelines should be adapted to the
ongoing CHMP procedure.

It is the responsibility of the OME Co to know where the product is in the procedure and what the
most recent discussions in the CHMP contain.
Step
Action
Responsibility
Presubmission phase of CHMP application
1
Inform D-DS-OME of upcoming CHMP application (initial MA or
PM
extension of indication) for an orphan indication (for initial MA
applications, see SOP/H/3004) and invite D-DS-OME representative
to a pre-submission meeting if needed.
2
If no longer available, coordinate appointment of EMA Co.
OME Asst
3
Attend pre-submission meeting and highlight to the sponsor
OME Co
procedure for review of orphan designation and requirement to
submit
a
maintenance
of
orpan
designation
report.
Major
anticipated maintenance issues may be flagged during the meeting.
After submission of CHMP application
4
Inform D-DS-OME of completed validation of the CHMP application.
PM
5
If not received, request the sponsor to submit the maintenance
OME Asst
report to D-DS-OME (at time of submission the CHMP application
for accelerated review or at day 121 of regular MA procedure)
(Template 1a).
6

On submission of the maintenance report, acknowledge receipt
OME Asst
(Template 2) informing about a possibility to hold a preassessment TC.

Download the sponsor’s maintenance report in DREAM.

Save in DREAM the review report (Template 3a) and the
presentation (Template 3b) templates and complete
administrative data.

Forward relevant DREAM links to the OME Co.
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Step
Action
Responsibility
7
Organise a monthly internal review of orphan designations meeting
OME Asst
inviting OME Cos
8
Examine the maintenance report, and notify the sponsor in writing
OME Co
of any major issues identified.
9
If requested by the sponsor, organise a pre-assesment TC to
OME Asst
discuss these issues.
10

Chair the orphan designation review pre-assessment TC with
OME Co
the sponsor.

When major issues are anticipated/identified, request from the
sponsor missing data.
11

Advice on the next steps of the review procedure.

Run SIAMED report on orphan products with on-going MA
COMP Sec
procedures.

Cross check status of procedures with the CHMP meeting
documents (agenda, draft summary of outcomes and annexes).

Update relevant COMP agenda listing including new CHMP
applications for orphan medicinal products.

Table the listing in MMD for forthcoming COMP meeting for
nomination of COMP coordinators.
Assessment / adoption of COMP opinion on review of
orphan designation
12

Attend monthly review of orphan designations meeting and
OME Co
discuss ongoing CHMP applications; if necessary, identify
experts or patient’s representatives and inform the COMP
secretariat accordingly.

Around day 150 for initial MA application and around day 90 of
accelerated procedure, draft the report on review of orphan
designation (Template 3a).

If major issues remain unaddressed request additional data
from sponsor ahead of the COMP discussion and request from
the sponsor the updated report (Template 1b).
13

Send the review report to COMP Co for comments. This should
OME Co
be done well before COMP pre-mailing corresponding to the
COMP meeting taking place prior to the CHMP meeting where
the product is scheduled for opinion, attach Template 4a.

Attend the summary report meeting to internally discuss the
draft review report.
14

Download COMP Co comments in DREAM and link in the review
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Step
Action
Responsibility
report.

Link the review report and presentation in the COMP meeting
folder.
15

OME Co
Discuss the report and product with the COMP Cos via
telephone or email.
16

Update the review report if necessary.

Prepare slides for the COMP plenary.

Insert product expected for adoption of an opinion at next
COMP Sec
CHMP meeting in COMP agenda for first discussion at the COMP
meeting.

Table in MMD review report from a shortcut to documents and
presentations folder where meeting documents are linked for
COMP meeting and mailings.

Table relevant CHMP assessment report.
17
Co-ordinate first discussion in the COMP meeting.
OME Co
18

If COMP trend is negative, go to step 19.
OME Co

If COMP trend is positive, go to step 35.
19

Co-ordinate adoption of LoQ by COMP.
OME Co
20

After the COMP meeting finalise the review report with the list
OME Co
of questions for sending to the sponsor.

Make sure any text copied from the CHMP assessment report
has been deleted.
21
Perform quality check of the review reports with LoQ.
OME HoO
22
Format and send the review report with LoQ (DREAM version label
OME Asst
“with list of questions”) to sponsor informing about deadline for
written
response
(two
weeks
before
next
COMP
meeting)
(Template 3c).
23
Include product with CHMP positive opinion adopted at last CHMP
COMP Sec
meeting for a second COMP discussion and/or an oral explanation
in COMP agenda for the next meeting (product with CHMP negative
opinion should also be included in COMP agenda for information
only).
24
Receive responses to LOQ and link in review reports (DREAM
OME Asst
version label “with response to LoQ”).
25
Forward responses to COMP Co with request for comments, attach
OME Asst
Template 4b.
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Step
Action
Responsibility
26
After discussion by CHMP on CHMP application:
OME Co

If CHMP outcome is negative, go to step 27.

If CHMP outcome is positive and a positive opinion is adopted,
go to step 30.
27

If CHMP adopts a negative opinion, go to step 28.

If the applicant withdraws the MA application before the CHMP
OME Co
adopts a negative opinion, there is no further need to review
the orphan designation and the procedure ends here.
28

If the applicant asks for a review of the CHMP negative opinion,
OME Co
put the OME second discussion by COMP on hold and go to step
29.

If the applicant does not request a review of the CHMP
negative opinion, there is no further need to review the orphan
designation and the procedure ends here.
29

If the outcome of the CHMP review is positive and a positive
OME Co
opinion is adopted, go to step 30.

If the outcome of the CHMP review is negative and a negative
opinion is adopted, there is no further need to review the
orphan designation and the procedure ends here.
30
Send to sponsor invititation to oral explanation to be held at the
OME Asst
COMP meeting following adoption of CHMP positive opinion
(Template 3c).
31
Update slides for the plenary discussion.
OME Co
32
Coordinate oral explanation and second discussion in the COMP
OME Co
meeting.
33
34

If COMP trend is negative, go to step 34.

If COMP trend is positive, go to step 35.

Inform sponsor of negative trend, and of regulatory options
OME Co
OME Co
and consequences (including appeal procedure, delay of
marketing authorisation decision by the EC).

If sponsor does not request a withdrawal of orphan designation
from EU Register, go to step 35.

If sponsor requests a withdrawal of orphan designation from EU
Register, inform PM and finalise the review report (version label
“final”), go to step 47.
35
Ensure adoption of grounds for review opinion.
OME Co
36
Inform PM of COMP opinion.
OME Co
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Step
Action
Responsibility
37

Go to SOP/H/3049 and follow steps in opinion phase.
OME Co/OME Asst

Return to this SOP and go to step 38.

If COMP opinion is positive, go to step 39.

If COMP opinion is negative, go to step 40.

Format review report and save (with DREAM version label
38
39
OME Co
OME Asst
“adopted”).

Send COMP positive opinion (Template 5a) to EC (Template
6a). Send COMP positive opinion and review report to sponsor
(Template 6b), go to step 47.
40
Forward review report with the grounds for negative opinion to AF-
OME HoO
LD and D-RS-REA for the check.
41
Send COMP negative opinion (Template 5b) and review report to
OME Asst
sponsor with information on possibility to appeal within 90 days of
receipt of opinion (Template 6c).
Appeal
42
43

Receive response from sponsor.

If sponsor appeals, go to step 43.

If sponsor does not appeal, go to step 46.

Go to SOP/H/3049 and follow steps in appeal phase.

Return to this SOP and go to step 44.
OME Co/OME Asst
OME Co/OME Asst
44
Inform PM of COMP opinion.
OME Co
45
Revise review report with outcome of appeal (version label
OME Co
“adopted post-appeal”).
46
Send final opinion to EC (Template 6a) and to sponsor (Template
OME Asst
6b in case of appeal (from step 45) or Template 6d in case of no
appeal (from step 42)).
Public summary of opinion
47
Refer to SOP/H/3371 for preparation of the public summary of
MHI writer/OME Co
opinion on the review of orphan designation at the time of
granting/varying a marketing authorisation.
48

Upon notification of EPAR publication send “Recommendation
OME Asst
for maintenance of orphan designation” to webteam for
publication.

Update product information sheet with details of the marketing
authorisation and trasmit to webteam for update for the
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Step
Action
Responsibility
relevant orphan webpage. (see SOP/H/3046).
10. Records
Records produced from this procedure are stored in accordance with WIN/H/3047.
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